This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Mutants of human gamma-D (HGD) crystallin are implicated in cataract formation. We have shown that R14C, a mutant form of HGD readily aggregates forming reducible intermolecular disulfide bonds. Cys14 introduced in the mutant in place of Arg, is the likely cause of such dramatic protein aggregation. The Cys-SH bond vibration is unequivocally determined in the Raman spectrum of proteins, and we have experimentally determined the SH contribution of Cys 14 in the Raman spectrum of the R14C mutant. Now, we would like to use ab-initio and DFT methods in order to model the Raman spectrum of Cys 14 to understand the chemical environment of the SH group, which not only determines its Raman frequency and intensity but may also influence its reactivity. Towards this goal, we would like to use software products such as Gaussian and Gamess available in the SGI machine POPEL. In a related project, we have identified the Raman SH bands of all the seven Cys residues individually in bovine gamma-B crystallin. Some of these Cys residues are known to react with glutathione, forming disulfide bonds and giving rise to the glutathiolated protein derivatives found normally in the lens. Here again, we would like to use ab-initio and DFT methods to calculate the Raman vibrational frequencies and intensities of protein-thiol -SH bonds. To facilitate the use of these theoretical methods, we already have available high-resolution x-ray crystal structures of these proteins. We propose using QM/MM methods whereby we would select a small region around the -SH group for the application of high-level theoretical methods and for the rest of the protein we would use MM methods using the AMBER forcefield.